Prevalence of Autoimmune Thyroiditis among Children with Autoimmune Hepatitis

doi:10.21203/rs.3.rs-2762498/v1

Background

Autoimmune hepatitis (AIH) is an organ specific autoimmune disease, which can manifest at any age of life. there is a high prevalence of extrahepatic autoimmune diseases in patients with AIH. Autoimmune thyroid diseases (ATDs) are the most frequent extrahepatic autoimmune disorders among patients with AIH. Aim of work is to detect the frequency of ATDs among Egyptian children with AIH.

Methods

This research is a cross-sectional study conducted on 58 children with AIH aged ≤ 18 years. All patients were tested for free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-TG). Thyroid ultrasound (US) and thyroid scan were performed for patients with abnormal thyroid profile, borderline values, positive anti-TPO or anti-TG.

Results

The mean ± standard deviation (SD) for the age of the patients was 11.3 ± 4.5 years. Out of 58 patients of AIH, 28 patients (48.3%) had associated other autoimmune diseases. Autoimmune thyroiditis was the most common associated autoimmune disease being present in 10 patients (17.2%). The thyroid status of AIT patients showed that 6 patients (60%) were euthyroid, 3 patients (30%) had subclinical hypothyroidism and only one patient (10%) was hyperthyroid.

Conclusion

Autoimmune hepatitis in Egyptian children is commonly associated with other autoimmune diseases. Autoimmune thyroiditis is the most common to be associated with AIH in pediatric patients. As it is not usually clinically manifesting, regular screening for AIT in children with AIH is mandatory.

autoimmune hepatitis

children

autoimmune diseases

autoimmune thyroiditis

Autoimmune hepatitis (AIH) is an organ specific autoimmune disease of unknown etiology that manifests as a chronic inflammatory disease of the liver, typically characterized by periportal inflammation, elevated autoantibodies and hypergammaglobulinemia (1). A variety of clinical presentations can be observed ranging from mild, almost subclinical disease to fulminant hepatitis (2,3). While the pathogenesis is not fully understood, the current hypothesis is that an environmental agent is thought to trigger a dysregulated T-cell response against autoantigens in genetically susceptible individuals (4).

There is a high prevalence of concurrent extrahepatic autoimmune diseases in children with AIH (42%) (5). It showed a significant association with autoimmune thyroid diseases (ATDs), followed by autoimmune skin disease, celiac disease, and vasculitis. All patients with an extrahepatic autoimmune disease should be assessed for the concomitant presence of an asymptomatic AIH (6). Autoimmune thyroid diseases (ATDs), including Hashimoto’s thyroiditis (HT), are common organ-specific autoimmune diseases that frequently coexist with other autoimmune disorders (7). They are the most frequent extrahepatic autoimmune diseases among patients with AIH (16.01%) (8,9).

Autoimmune thyroid diseases (ATDs) are the most common thyroid disorders in pediatrics and adolescence (10). Patients may be euthyroid, or have subclinical or overt hypothyroidism depending on the severity of the immunologic damage (11). The most common age at presentation is adolescence, but the disease may occur at any time, rarely even in children under one year of age (12).

Children and adolescents are mostly asymptomatic; the majority are female, pubertal and euthyroid. Diagnosing at an early stage offers the opportunity for a timely intervention (13).

Measurement of the serum thyroid stimulating hormone (TSH) concentration is the best initial screening test for the presence of primary hypothyroidism. If the TSH is elevated, then evaluation of the serum free tetraiodothyronine (FT4) concentration will distinguish whether the child has subclinical (normal FT4) or overt (low FT4) hypothyroidism (13). A diagnosis of autoimmune thyroiditis (AIT) is made by the demonstration of an elevated concentration of anti-thyroglobulin antibodies (anti-TG Abs) and/or antithyroid peroxidase antibodies (anti-TPO Abs) in serum (11,14).

The aim of this study was to screen children with AIH to detect the frequency of associated AIT. Our secondary objective was to correlate AIT with AIH activity.

This cross-sectional study was conducted at two Pediatric Hepatology centers (Beni-Suef University Hospital & Cairo University Hospital, Egypt). The study included all children with established diagnosis of AIH ≤ 18 years of both sexes either they were newly presenting cases or old cases coming for follow up from September 2021 to October 2022. This research was approved by the Research Ethics Committee Review Board of Faculty of Medicine, Beni-Suef University (Approval NO: FMBSUREC/30042019). An informed consent from all the study patients or their guardians was taken prior to data collection. Confidentiality on handling the database was guaranteed. Privacy of participants was ensured.

Patients with other associated chronic liver diseases rather than AIH as chronic hepatitis B or C were excluded. All Metabolic liver diseases as Wilson disease were also excluded. Patients who had chromosomal disorders as Down, Klinefelter or Turner syndrome or who are treated with medications affecting thyroid function e.g., amiodarone, lithium or interferon alpha were also excluded.

The collected data included the following:

1) History taking: Personal and demographic data: name, age, sex and residency, symptoms suggestive of other autoimmune diseases, manifestations of AIT and current treatment for AIH. Family history: including parents' consanguinity, history of similar conditions or other autoimmune diseases in the family.

2) Examination

Vital signs at the time of study enrollment. Anthropometric measurements at the time of study enrollment including weight, height, and body mass index. They were plotted on Egyptian growth curves (15). Thorough examination of the thyroid gland. Complete abdominal examination for hepatomegaly, splenomegaly, and ascites. General examination for any stigmata of liver cell failure

3) Investigations (were performed at time of study enrollment):

Basic labs: complete blood count and full liver function tests. Investigations specific for AIH: serum total immunoglobulin G (IgG) and autoantibodies: anti-nuclear antibody (ANA), anti-smooth muscles antibody (ASMA), anti-liver kidney microsomal antibody type 1 (LKM-1), anti-mitochondrial antibody (AMA) and anti-neutrophil cytoplasmic antibody (ANCA). The type of AIH was determined according to the associated positive antibodies at presentation where ANA and /or ASMA are positive in AIH-1 and anti-LKM-1 is positive in AIH-2. Seronegative AIH is diagnosed by liver biopsy and exclusion of other causes of hepatic affection. Typical findings of histology include interface hepatitis, emperipolesis, hepatic rosette formation, Kupffer cell hyaline granules, prominence of plasma cells in portal tracts, and plasma-lymphocytic inflammation (16) .

Complete biochemical remission is defined as normalization of both serum ALT and IgG levels while histological remission involves the disappearance of interface hepatitis (16).

Thyroid workup: quantitative measurement of FT3 (Diasino®, REF: DS177704, Zhengzhou, China), FT4 (Diasino®, REF: DS177705, Zhengzhou, China), TSH (Diasino®, REF: DS177701, Zhengzhou, China), anti-TPO (EDI™, REF: KT 833, San Diego, USA) and anti-TG (EDI™, REF: KT 832, San Diego, USA) were done using Enzyme Linked Immuno-Sorbent Assay technique (ELISA). A peripheral venous blood sample (5 ml) was collected under complete aseptic conditions from all patients on plane tubes while they were on AIH treatment either steroids alone or steroids and immunosuppressives. Serum was separated from the blood after clotting and centrifugation. The serum samples were stored at -20°C.

Enzyme Linked Immuno-Sorbent Assay (ELISA) technique principle for FT3 and FT4 detection was competition principle. While sandwish technique was performed for TSH, anti-TPO and anti-TG detection.

Thyroid ultrasound and thyroid scan were done for patients with manifestations of thyroid affection, abnormal thyroid profile, borderline values, positive anti-TPO or anti-TG antibodies.

A case is defined as having AIT if anti-TPO and/ or anti-TG antibodies are positive (11,14,17,18) and by a typical hypo-echogenic and heterogeneous ultrasound pattern (14,18). Subclinical hypothyroidism is defined as high TSH with normal FT4 while overt hypothyroidism is defined as high TSH with low FT4 (17). Subclinical hyperthyroidism is defined as low TSH with normal FT4 while overt hyperthyroidism is defined as low TSH with high FT4 (18).

Statistical methods:

Data were collected and tabulated. Statistical Package for Social Science (SPSS) program version 22 was used for data analysis. Mean and standard deviation (SD) or median and interquartile range (IQR) were estimates of quantitative data as age and laboratory parameters, while frequency and percentage were estimates of qualitative data as sex and associated autoimmune diseases. Differences in biochemical characteristics were tested by Student’s unpaired t-test, Mann-Whitney U test or Wilcoxon test for quantitative data and by Chi-square test for qualitative data. A two-sided P value < 0.05 is considered statistically significant.

This cross-sectional study included 58 children with AIH. Forty patients (69%) were females with female to male ratio of 2.2:1. Mean ± SD for their age at the time of study enrollment was 11.3 ± 4.5 years, ranging from 1.5 to 18 years.

At presentation, jaundice was the most frequent symptom (81%), followed by dark urine (79.3%), abdominal pain (51.7%), malaise (51.7%) and bleeding (50%) .

Symptoms and signs suggestive of hypothyroidism included cold intolerance (6.9%), bradycardia (5.2%) and goiter (1.7%). Symptoms and signs suggestive of hyperthyroidism included tachycardia (8.6%), hyperactivity (3.4%), hyperthermia (1.7%), heat intolerence (1.7%) and goiter (1.7%).

Symptoms and signs suggestive of other autoimmune diseases included arthralgia (39.7%), skin rash (22.4%), hair loss (17.2%), chronic diarrhea (13.8%), oral ulcers (8.6%), joint swelling (6.9%), malar rash (5.2%) and photosensitivity (5.2%). Mucocutaneous candidiasis was only present in one patient (1.7%). None of the patients had hematuria or pretibial myxedema.

Family history of autoimmune diseases in first-degree relatives was reported in 11 patients (19%) including AIH, AIT, rheumatoid arthritis (RA), systemic lupus erythematosis (SLE), type I diabetes mellitus (DM), sclerosing cholangitis, familial mediterinian fever (FMF) and alopecia areata.

At the time of study enrollment, all patients had normal heart rate except 5 patients (8.6%) had tachycardia and 3 patients (5.2%) had bradycardia. Three patients (5.2%) had tachypnea and 5 patients (8.6%) had fever. Fourteen patients (24.1%) had systolic blood pressure above 95th percentile and 12 patients (20.7%) had diastolic blood pressure above 95th percentile.

Mean ± SD of body weight at the time of study enrollment was 38.7 ± 18.3 kg ranging from 7.5-83 kg with 10.3% below 3^rd percentile. Mean ± SD of height was 133.3 ± 23.3 ranging from 70-171 cm with 20.7% below 3^rd percentile. Mean ± SD of BMI was 20.4 ± 4.7 Kg/m²ranging from 12.6-32.4 Kg/m²with 3.4% below 3^rd percentile. Only one patient (1.7%) had overweight, and two patients (3.4%) had BMI > 97th percentile.

Hepatomegaly was detected in 32 patients (55.2%) and 5 patients (8.6 %) had ascites. One patient (1.7%) had goiter. None of the patients had exophthalmos.

Forty patients (69%) had type I AIH (positive ANA and/or ASMA), 15 patients (25.9%) had type II AIH (positive anti-LKM-1 antibody) while 3 patients (5.1%) had seronegative AIH.

At the time of study enrollment; 28 patients (48.3%) were in activity (out of them 7 patients were newly diagnosed cases) while 30 patients (51.7%) were in biochemical remission, out of them 13 patients achieved both biochemical and immunological remission.

To screen for associated AIT; FT3, FT4, TSH, anti-TPO and anti-TG were done for all patients. Table 1 shows the results of thyroid profile done for all patients. Figure (1) shows that 19 patients (32.8%) had thyroid abnormalities either in thyroid profile, autoantibodies, thyroid US or thyroid isotopic scan. Out of the 19 patients with thyroid abnormalities, 10 patients (52.6%) were diagnosed as AIT.

Out of 9 patients (15.5%) who were not diagnosed as AIT: 6 patients (66.7%) had subclinical hypothyroidism. One patient (11.1%) with subclinical hyperthyroidism (low TSH with normal FT4) with negative anti-TPO and anti-TG antibodies. One patient (11.1%) with normal thyroid gland US but with abnormal thyroid scan showing mild diffuse goiter with normal uptake, normal thyroid profile and negative autoantibodies. Another patient (11.1%) with mildly enlarged gland in US and thyroid scan showing mildly enlarged gland with fine nodular goiter and normal thyroid uptake.

Thyroid status of AIT patients showed that 6 patients (60%) were euthyroid, 3 patients (30%) had subclinical hypothyroidism and only one patient (10%) had overt hyperthyroidism. Thyroid-stimulating hormone receptor antibody (TRAB) was done for the patient with hyperthyroidism and it was 3 times the upper reference limit, so this patient was diagnosed to have Graves disease (GD). Other 9 patients were diagnosed as HT. Table 2 describes the clinical, autoimmune profile and AIH disease activity of children with associated AIT.

Methimazole, antithyroid drug, was started for the patient with GD. None of the patients with HT developped overt hypothyroidism during study period, so no hormonal replacement was started.

Patients with and without AIT were compared as regards demographic, clinical, and laboratory data (Table 3). Of all symptoms and signs suggestive of thyroid dysfunction, the following manifestations were the only statistically present in patients with AIT: goiter (p value = 0.027), hyperthermia (p value = 0.027) and heat intolerance (p value = 0.027).

AMA was significantly more prevalent in patients with AIT (p value = 0.027) (Table 3). There was no statistically significant difference between the two groups regarding AIH activity raising the importance of screening for associated AIT for all patients with AIH even if they are in remission.

We found that out of 58 patients of AIH, 28 patients (48.3%) had other comorbid autoimmune disorders. Seven patients had 2 associated autoimmune disorders and one patient had 3 associated autoimmune disorders thus raising the total number to 37 associated autoimmune disorders in 28 patients as shown in Table 4. The most common autoimmune disease in children with AIH was AIT (17.2%).

Like other autoimmune diseases, AIH can be associated with one or more autoimmune disorders either organ-specific or non-organ specific. Different studies estimated the frequency of the association of AIH and AIT in adult patients and it is around 10% (19). The aim of our study was to detect the frequency of AIT among Egyptian children with AIH.

History of an autoimmune disease in the patient himself or in any of the family members can be a clue in the diagnosis of AIH. In our study, family history of autoimmune diseases was reported in 11 patients (19%). Concomitant autoimmune diseases in the patients were reported in 28 patients (48.3%). Khoury et al reported concomitant autoimmune diseases in 20 and 50% of adult and pediatric AIH patients respectively (3). Meanwhile, other authors reported associated autoimmune disease in 23.5% of patients in their study (20).

In our study, AIT was the most common associated extrahepatic autoimmune disease with AIH as it was detected in 10 children (17.2%). Similarly, several studies reported that AIT was the commonest extrahepatic autoimmune disease associated with AIH (including HT, GD and unspecified autoimmune thyroiditis) (6,9,21,22,23). This demonstrates the importance of screening of AIH patients for early detection of associated AIT.

Growth failure is a common problem and multifactorial in many children with chronic diseases including children with chronic liver disease. Twelve patients (20.7%) in the current study had short stature with height < 3rd percentile for age; 2 of them were diagnosed as AIT. Previous researchers reported that important contributory factors to growth failure in these patients include increased energy needs, increased energy loss, malabsorption, decreased energy intake, anorexia, pain, vomiting, and inflammatory cytokines. Oral corticosteroids therapy is known to be associated with a delay in growth and puberty in children (24,25).

In the present study, AIT was more common in type I AIH than type II although the difference was not statistically significant. However, A previous report demonstrated that AIT was more common in type 2 AIH (26).

Sixty percent of our patients with AIT were euthyroid while 30% had subclinical hypothyroidism and only 10% had hyperthyroidism, this explains the importance of screening for AIT in AIH patients even if there are no symptoms or signs suggestive of thyroid affection as most patients are euthyroid. Similarly, Wasniewska and co-authors discovered that 52.1% were euthyroid, 19.2% had subclinical hypothyroidism, 22.2% had overt hypothyroidism and only 6.5% had hyperthyroidism (27). This high percentage of euthyroid AIT in AIH patients emphasizes the importance of AIT screening in AIH patients.

Some previous investigators reported different results as 21% were euthyroid, 42% had subclinical hypothyroidism and 37% had overt hypothyroidism (28).

Out of our 10 patients with AIT, only one patient (10%) had GD and the other 9 patients (90%) had HT. This was in accordance with Aversa et al who reported that GD is much less common than HT, especially in pediatric age (29). Moreover, Salerno et al stated that HT is the commonest form of thyroiditis in pediatric age (30).

In most chronic illnesses, defects arise in thyroid hormone metabolism, resulting in the sick euthyroid syndrome or non-thyroidal illness. This is characterized by a normal total T4, normal/high FT4, low total T3, low FT3 and an elevated reversed T3 (rT3) (31). Similarly, Huang and Liaw reported that liver diseases are frequently associated with thyroid test abnormalities or dysfunctions, particularly elevation of thyroxine-binding globulin and thyroxine (32).This mechanism can explain the abnormal thyroid profile found in our patients who did not have AIT. TSH secretion may be transiently suppressed because of other causes such as euthyroid sick syndrome or concomitant use of TSH-suppressing drugs, e.g., steroids (18). Neglect of these facts may result in misdiagnosis of associated thyroid diseases and thereby cause errors in patient care.

We found that there was statistical significant difference between patients with and without AIT as regarding goiter (p value = 0.27), hyperthermia (p value = 0.27) and heat intolerance (p value = 0.27) but all other symptoms and signs of thyroid affection showed no statistical significant difference meaning that screening for all AIH patients is essential even if they are asymptomatic.

In the light pf our results, We emphasize on the importance of screening of AIT in any child with AIH even if patient is not symptomizing or even in remission.

The main limitation of our study is the relatively small number of included patients and the cross-sectional nature of the study design. Despite these limitations, this study represents one of the largest studies performed on pediatric patients with AIH in Egypt.

Autoimmune hepatitis in Egyptian children is commonly associated with other autoimmune diseases. Autoimmune thyroiditis is the most common to be associated with AIH in pediatric patients. As it is not usually clinically manifesting, regular screening for AIT in children with AIH is mandatory.

Ethics approval and consent to participate:

Ethical approval was obtained from the ethical committee, Faculty of Medicine, Beni-Suef University. Approval NO. FMBSUREC/30042019. Written informed consent was taken from the participants. The study was performed following the principles of the Declaration of Helsinki.

Consent for publication:

Not applicable

Availability of data and materials:

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests:

The authors declare that they have no competing interests.

Funding:

This research did not receive any specific grant from public, commercial or not-for-profit funding agencies.

Authors' contributions:

EA contributed to the study conception and design. HMS contributed to the study conception and design . DS revised the manuscript. HMA contributed to material preparation, data collection. RAM made the laboratory work . RAA contributed to first draft of the manuscript, the study conception and design. MH contributed to the study conception, design, material preparation, data collection and first draft of the manuscript. All authors read and approved the final manuscript.”.

Acknowledgements:

Not applicable.

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Table 1: Mean ± SD for thyroid profile and autoantibodies done for 58 AIH patients

Parameter	Normal range	Result Mean ± SD or Median (IQR)	Min-Max	Number of patients with increased level (%)	Number of patients with decreased level (%)
Free T3	3.3-7.5 pmol/L	4.6 (0.6)	3.1 – 71.7	1 (1.7)	0 (0)
Free T4	11.5-23.8 pmol/L	20 ± 8.8	13.3 – 63	1 (1.7)	0 (0)
TSH	0.37-5.10 μIU/mL	3.3 ± 1.9	0 – 9.1	9 (15.5)	2 (3.4)
Antithyroid peroxidase	≤ 35 U/mL	12.8 (14.6)	2.1 – 102	8 (13.8)
Antithyroglobulin	≤ 50 U/mL	25 (21.8)	8.3 – 105	6 (10.3)

SD: Standard deviation, T3: Triiodothyronine, T4: Tetraiodothyronine, TSH: Thyroid stimulating hormone.

Table 2: Age, sex, AIH status, thyroid status and thyroid radiological findings of AIT patients

Pt	Age (ys)	Sex	AIH status	Free T3	Free T4	TSH	Thyroid status	Anti-TPO	Anti-TG	Thyroid US	Thyroid scan
1	10	F	Activity	N	N	↑	Subclinical hypo-thyroidism	+ve	+ve	Slightly enlarged in size with hypo-echogenic and heterogeneous echogenicity.	Chronic thyroiditis with spotty uptake of radioactive iodine.
2	13	F	Activity	N	N	↑	Subclinical hypo-thyroidism	+ve	+ve	Diffusely mildly enlarged gland with a hypo-echogenic and heterogeneous echotexture.	Hyper-functioning gland.
3	7	M	Biochemical remission	↑	↑	↓	Overt hyper-thyroidism	-ve	+ve	Heterogeneous echo structure with diffuse hypoechogenicity.	Hyper-functioning gland.
4	9	F	Biochemical remission	N	N	N	Euthyroid	+ve	-ve	Heterogeneous echo structure with patcy hypoechogenicity.	Hyper-functioning gland.
5	17	F	Biochemical remission	N	N	N	Euthyroid	+ve	-ve	Heterogeneous echo structure with patchy hypoechogenicity.	Not done due to parental refusal.
6	15.5	F	Biochemical remission	N	N	N	Euthyroid	+ve	-ve	Heterogeneous echo structure with diffuse hypoechogenicity.	Hyper-functioning gland.
7	18	M	Activity	N	N	↑	Subclinical hypo-thyroidism	-ve	+ve	Mild diffuse enlargement with diffuse hypoechgenicity and heterogenous echotecture.	Mild diffuse goiter with hyper-functioning gland.
8	12	F	Activity	N	N	N	Euthyroid	+ve	-ve	Slightly enlarged in size with hypo-echogenic and heterogeneous echogenicity.	Relatively low homogenous thyroid uptake.
9	12	F	Activity	N	N	N	Euthyroid	+ve	+ve	Diffusely mildly enlarged gland with a hypo-echogenic and heterogeneous echotexture.	Hyper-functioning gland.
10	11	F	Activity	N	N	N	Euthyroid	+ve	+ve	Moderate diffuse enlargement with diffuse hypoechogenicity and heterogenous echotecture.	Diffuse enlargement with normal thyroid uptake.

AIH: Autoimmune hepatitis; AIT: Autoimmune thyroiditis; Anti-TG: Antithyroglobulin; Anti-TPO: Antithyroid peroxidase; F: Female; M: Male; N: Normal; Pt: Patient; T3: Triiodothyronine; T4: Tetraiodothyronine; TSH: Thyroid stimulating hormone; US: Ultrasound; ↑: Increased above normal level; ↓: Decreased below normal level; -ve: Negative; +ve: Positive.

Table 3: Comparison between AIH patients with and without associated AIT

Parameters	Patients without AIT N= 48	Patients with AIT N= 10	Total P-value	Detailed P-value
Sex: N (%) Females Males	33 (68.7) 15 (31.3)	8 (80) 2 (20)	0.48
Age in years; mean ± SD	11 ± 4.7	12.5 ± 3.5	0.37
Age of onset in years; mean ± SD	6.6 ± 4.1	8.3 ± 3.3	0.22
Mode of presentation: N (%) Acute hepatitis Insidious onset Acute liver cell failure Complications of chronic liver disease	24 (50) 7 (14.6) 10 (20.8) 7 (14.6)	7 (70) 1 (10) 1 (10) 1 (10)	0.69	0.23 0.69 0.42 0.69
Symptoms & signs of thyroid affection Goiter Hyperthermia Heat intolerance	0 (0) 0 (0) 0 (0)	1 (10) 1 (10) 1 (10)	0.027* 0.027* 0.027*
Positive family history of AIH	3 (6.3)	1 (10)	0.54
Positive family history of AIT	2 (4.2)	1 (10)	0.44
Family history of ADs	8 (16.7)	3 (30)	0.32
Autoimmune disease association	18 (37.5)	3 (30)	0.65
Weight in Kg < 3^rd percentile	6 (12.5)	0 (0)	0.23
Weight > 97^th percentile	1 (2.1)	0 (0)	0.62
Height in cm< 3^rd percentile	10 (20.8)	2 (20)	0.92
Height > 97^th percentile	1 (2.1)	0 (0)	0.62
BMI kg/m²< 3^rd percentile	2 (4.2)	0 (0)	0.48
BMI > 97^th percentile	1 (2.1)	1 (10)	0.23
Total Ig G at presentation	2755.5 ± 1208	3200.1 ± 440.7	0.41
Total Ig G at study enrollment	1819.7 ± 1208.7	1866 ± 805.7	0.66
Positive ANA at study enrollment	6 (12.5)	0 (0)	0.58
Positive ASMA at study enrollment	23 (47.9)	6 (60)	0.49
Positive anti-LKM antibody at study enrollment	7 (14.6)	0 (0)	0.19
Positive AMA at study enrollment	0 (0)	1 (10)	0.027^*
Positive ANCA at study enrollment	4 (8.3)	1 (10)	1
Type of AIH: Seronegative Type I Type II	2 (4.2) 32 (66.7) 14 (29.2)	1 (10) 8 (80) 1 (10)	0.35	0.42 0.42 0.19
Remission at study enrollment	26 (54.2)	4 (40)	0.42
Activity at study enrollment	22 (45.8)	6 (60)	0.42

ADs: Autoimmune diseases, AIH: Autoimmune hepatitis, AIT: Autoimmune thyroiditis, AMA: anti-mitochondrial antibodies, ANA: anti-nuclear antibody, ANCA: anti-neutrophil cytoplasmic antibodies, Anti-LKM-1: anti-liver kidney microsomal type 1 antibody, ASMA: anti-smooth muscle antibody, BMI: Body mass index, IgG: immunoglobulin G, SD: Standard deviation, T3: Triiodothyronine, T4: Tetraiodothyronine, TG: Thyroglobulin, TPO: thyroid peroxidase, TSH: Thyroid stimulating hormone. Chi Square, Mann Whitney and independent sample t tests are used. P value is significant at level< 0.05.

Table 4: Frequency of other autoimmune diseases in children with AIH (n=58)

Associated autoimmune diseases	N (%)
Hepatobiliary & gastrointestinal tract
Primary sclerosing cholangitis	7 (12.1)
Ulcerative colitis	2 (3.4)
Crohnʼs disease	1 (1.7)
Celiac disease	1 (1.7)
Endocrinal
Autoimmune thyroiditis	10 (17.2)
Type I DM	1 (1.7)
Rheumatological
SLE	5 (8.6)
FMF	1 (1.7)
Skin
Alopecia	6 (10.3)
Vitiligo	1 (1.7)
Psoriasis	1 (1.7)
Discoid lupus erythematosus	1 (1.7)

AIH: Autoimmune hepatitis, DM: Diabetes mellitus, FMF: Familial medeterinian fever, SLE: systemic lupus erythematosus.

Prevalence of Autoimmune Thyroiditis among Children with Autoimmune Hepatitis

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Abstract

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Introduction

Patients And Methods

Statistical methods:

Results

Discussion

Conclusion

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Status:

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